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Volume 2012, Article ID sjeer-109, 5 Pages, 2012. doi: 10.7237/sjeer/109
Research Article
Ochratoxin a: Any Cause for Concern in Sub Saharan Africa?
Felixtina Jonsyn-Ellis (PhD)
Njala University
School of Environmental Sciences
Njala, Sierra Leone P.M. Bag Freetown
Accepted 17�� May 2012
INTRODUCTION
ABSTRACT
Ochratoxin A (OTA) is an important secondary metabolite of
different Aspergillus and Penicillium species. OTA is
immunosuppressive, teratogenic, mutagenic and carcinogenic in
most animal species and as a result it is classified by the
International Agency for Research on Cancer (IARC) as a group 2Ba possibly carcinogen to humans. OTA was first discovered in South
Africa but while this toxin is well known and documented in
Europe and North America, resulting in the establishment of
stringent regulations and measures to prevent it from reaching the
food chain, there is a dearth of information on OTA in sub-Saharan
Africa (SSA). With the exception of North African countries and a
few countries in SSA little or no information is available on the
prevalence of OTA in other African countries. This review is not
only to highlight the significance of OTA to SSA, where this toxin
has been found as a natural contaminant in several indigenous
foodstuffs but also to show evidence of the widespread ingestion
of this toxin, as has been determined in body fluids of peoples in
North Africa and even in young children in Sierra Leone. The
attention of African Governments, NGOs and scientists is drawn to
the issue of ochratoxin A in the food chain with some pertinent
recommendations made.
Ochratoxins are secondary metabolites of several
Aspergillus species, Penicillium verrucosum and Penicillium
nordicum [1]. Ochratoxin A was first isolated in 1965 from
cultures of Aspergillus ochraceus [2] now known as A.
alutaceous. The Ochratoxins, A, B and C occur naturally and
are essentially phenylalanine derivatives of an isocoumarin
nucleus [3]. Chemically, they are composed of a 3, 4 dihydro3 methylisocoumarin moiety linked via the 7-carboxy group
to L-B-phenylalanine by an amide bond. The chlorine
containing metabolite, designated Ochratoxin A is the major
component of extracts from A. ochraceus [2]. OTA is the
most prevalent toxin and is classified as a group 2b potential
human carcinogen by the International Agency for Research
on Cancer [4]
Ochratoxin A has been shown to be a potent nephrotoxin in
all animal species tested with the exception of mature
ruminants [5]. It has also been shown to be carcinogenic,
teratogenic , mutagenic and immunosuppressive [6]
KEYWORD: Ochratoxin A, Sub-Saharan Africa, Foodstuffs,
Body fluids
Figure 1. Chemical structures of the Ochratoxins
Corresponding Author:Felixtina Jonsyn-Ellis (PhD)
Njala University School of Environmental Sciences Njala, Sierra Leone P.M. Bag Freetown
Email: tinajonsyn@yahoo.com
Page 2
OCCURRENCE OF OCHRATOXIN A:
Despite the acknowledged ubiquity of A. ochraceus,
widespread across temperate and tropical regions, it is
mostly referred to in the literature as occurring in temperate
or continental climates [6] and as such its presence in Africa
was not until recently fully recognized. Initially, the
presence of OTA was mainly reported from European and
North American Countries primarily in the wheat and barley
growing areas [3] even though it was first discovered in
South Africa [2]. Data related to the levels of OTA
contamination in foods and feeds from tropical Africa is very
limited. A. ochraceus has been found as a co-contaminant in
a variety of foodstuffs examined in Sierra Leone, such as
sesame seeds (beni seeds) maize, fermented cassava ("dry
ball Foofoo") "ogiri" (fermented sesame seeds), broad beans,
dried red pepper and smoke dried fish. Semi- quantitative
analyses of these foodstuffs have shown that in most cases,
OTA is present in appreciable quantities [7-10] In a
preliminary survey of foods and feedstuffs from Senegal,
Kane and colleagues [11] established levels of 34 ppb OTA
in cowpeas. Aflatoxin was also detected in almost all
samples, suggesting a competition between aflatoxin
producing and Ochratoxin producing moulds [11]. In an
earlier study in Nigeria, Adekunle and Ayeni [12] isolated
A. ochraceus in most foodstuffs examined. In another study
in Nigeria, even though A. ochraceus was not isolated in
maize samples, OTA and Aflatoxin B1 were detected [13].
Recent studies on rice from Nigeria have shown the
presence of OTA in 66.7% [14] and 98% [15] of rice samples
from Lagos markets and Niger State respectively. There was
also a wide gap in the levels detected in the two studies.
Adejuyo and colleagues detected low levels of OTA (0.012.18 ng g-1) whereas Makum and colleagues detected levels
as high as 134 - 341ug/kg.
Cola nuts (Cola nitida) from Nigeria have been shown to
contain OTA. Levels as high as 65.3ug/kg and 19.1ug/kg
have been recorded in white and red cola nuts respectively
[16]. The extensive exportation of coffee and cocoa beans
to the European union, from tropical Africa, has necessitated
a number of studies on the quality of these products .In one
such study, it was determined that out of 162 samples of
green coffee beans from different countries, the African
samples were highly contaminated with OTA [17]. In North
African countries where there is a prevalence of
nephropathy and kidney problems, high levels of OTA has
been detected in maize, rice, wheat and lentils [18-20] In
South Africa, wine has been extensively studied for the
presence of OTA. This toxin was detected in 15 white wines
at level of >0.01 ug/l with a mean of 0.16ug/l and 9 red
wines - mean 0.24ug/l [21].
OCHRATOXIN AND DISEASE
Ochratoxicosis
There are no reports in the literature of acute ochratoxicosis
in humans. Ochratoxicosis appears to be well established
disease entity in poultry and to a lesser extent in swine [22].
The immune suppressive nature [23] Anemia [24],
nephropathy [25], teratogenicity [26] and carcinogenicity
Science Journal of Environmental Engineering Research(ISSN:2276-7495)
[27] of Ochratoxin A has been determined and documented
in a number of animal species.
OCCURRENCE OF OTA IN HUMANS
Ochratoxin A is found in blood bound to serum albumin[28]..
Low molecular weight species pass the glomerular
membrane and accumulate in the kidneys and the highest
concentrations of OTA are found in these tissues[29].
Ochratoxin A has a half-life of about 35 days in humans and
since OTA binds readily to serum albumin, the blood
concentrations are considered to represent a convenient
biomarker of exposure [30] Several studies have been
carried out in European countries and Canada, in order to
examine human exposure to this toxin. OTA was detected
in blood samples of healthy person at varying frequencies
and levels [31] With the exception of some North African
countries, comprehensive studies on ochratoxin levels in
human body fluids, such as blood and urine samples. have
only been conducted in Sierra Leone. Sangare-Tigori and
colleagues [32] examined human sera in Abidjan, Ivory
Coast for ochratoxin A. It was detected that 34.9% of healthy
donors, had OTA concentrations ranging from 0.01 - 5.81
ug/l. whereas 20.5% nephropathy patients undergoing
dialysis were OTA positive at levels of 0.167-2.42 ug/l. The
nephrotoxic effect of ochratoxin A is detectable by urinary
analysis, but this is relatively non-specific. Similarly,
anaemia is an early manifestation but is also non-specific,
and it is difficult to use this parameter for early diagnosis of
the ailment. Ochratoxin A has been found in human milk
samples in several European countries [31] Data on the
presence of this toxin in Breast milk samples from Africa is
very scarce. Two studies from Egypt [33, 34] have detected
levels as high as 45ng/ml and 189ng/ml. Our study in Sierra
Leone have shown considerably high levels - up to 337ng/ml
in one sample [35].
OCHRATOXIN A AND HUMAN HEALTH
Unlike aflatoxin which has been implicated in several
diseases such as primary liver cancer, Reye's syndrome and
Kwashiorkor, OTA has only been implicated in the aetiology
of Balkan Endemic Nephropathy (BEN) and Urinary Tract
Tumours (UTT). Endemic nephropathy is a fatal human
renal disease, affecting predominantly rural populations in
the central Balkan Peninsula. So far, the disease has been
reported in Bosnia and Herzegovina, Bulgaria, Croatia,
Romania, and Yugoslavia (Serbia)[36] Striking similarities
between the changes in the renal structure and function
found in endemic nephropathy and in ochratoxin A-induced
porcine nephropathy suggested a common causal
relationship. Epidemiological similarities, in particular the
endemic occurrence support the hypothesis that ochratoxin
A is a causative agent of endemic nephropathy in
humans[37]. Even though ochratoxin was first discovered
and documented by South African scientists [2], unlike
aflatoxins there is a dearth in research relating to
ochratoxin and human health in Africa. The association
between the presence of OTA and nephropathy in Africa has
been implied in only a few studies. With the exception of
some North African Countries [18-20; 37, 38] and Senegal
How to Cite this Article: Felixtina Jonsyn-Ellis , “Ochratoxin a: Any Cause for Concern in Sub Saharan Africa? ,”Science Journal of Environmental Engineering Research,
Volume 2012, Article ID sjeer-109, 5 Pages, 2012. doi: 10.7237/sjeer/109
Science Journal of Environmental Engineering Research(ISSN:2276-7495 )
[11], very little information on disease related to OTA
ingestion has been documented in other African countries.
A high prevalence of nephropathy has been reported in
Tunisia [18] and Algeria [19]. Recently, it has been reported
that over two million young people of both genders are
suffering from kidney problems (nephropathy) of unknown
aetiology in Morocco [39] In Senegal, chronic renal failure
accounted for 87.6% of all deaths from urogenital disease
[11]. It was discovered that in countries were BEN is
present; there was an unusually high prevalence of urinary
tract tumours [40]. In the North African countries, in which
human nephropathy similar to BEN is observed, the disease
has been tentatively called chronic interstitial nephropathy
(CIN) [40]. Like BEN, the causative role of ochratoxin A in
CIN is very controversial. Results of two studies from
Tunisian researchers [33, 42] have clearly indicated that
there is causal uncertainty. It could be assumed that just like
BEN, CIN could develop as a result of OTA acting
synergistically with other environmental toxins. Wafa and
colleagues [43] reported that levels of OTA were higher in
a sample of Egyptians patients with urinary tract tumours
-UTT than on healthy controls. The presence of OTA in
breast milk, cord blood, serum, urine and stool samples from
Africa, could predispose the kidneys to renal disease early
in life.
METABOLITES OF OCHRATOXIN A IN BODY FLUIDS
Page 3
4R- Hydroxyochratoxin A (4R -OTA) has been detected in
several studies of urine and stool specimens from infants
and school children in Sierra Leone. While the parent toxin
- OTA was only detected in 27% and 23% of urine samples
of boys and girls during the rainy season, 4R -OTA was
detected in 29% and 52% respectively, during this same
period. Similarly, dry season samples contained OTA in 21
%( boys) and 31% (girls) and 4R -OTA in 37% (boys) and
38% (girls) [45]. Urine samples of 54 infants - 24 girls and
30 boys also showed that while the parent toxin was only
detected in 3% and 33% (girls and boys) respectively, 4R
-OTA was detected in 50% (girls) and 40% (boys) [46]
Examination of stool specimens of 32 infants revealed the
presence of OTA in 33% at concentration ranges of 0.114ng/ml and 4R -OTA in 46% at concentration ranges of
0.2-2.5ng/ml [46] Although 4R -OTA is considered less toxic
than ochratoxin A [47] its presence in higher frequencies in
urine and stool specimens examined is an indication of the
presence of the parent toxin. Castegnaro and colleagues [48]
however failed to detect this metabolite in human urine. One
reason that could be advanced for the failure of detection of
4R -OTA was that their subjects suffered from Balkan
Endemic Nephropathy with presumably damaged kidneys
while subjects from Sierra Leone were young and had
healthy kidneys capable of excreting the metabolite. Like
Ochratoxin B which often co-occurs in foodstuffs, urine and
stool specimens examined, 4R -OTA is believed to have an
ameliorating effect on the toxicity of OTA [47]
OTA is converted by cytochrome P450 (CYP450) enzymes
resulting in the production of 4R-OH-OTA and 4S OH-OTA
[44].
Figure 2. Chemical structure of a derivative of OTA
CONCLUSION:
There is paucity of data on ochratoxin A in foodstuffs in
African countries and even more importantly, data on
dietary exposure through assessment of body fluids, is with
the exception of North African countries and Sierra Leone,
non-existent. Apart from the cocoa and/or coffee growing
African countries which will ultimately be made aware of
the presence and levels of OTA on these commodities by
importing nations, such as EU countries, other African
countries must endeavour to establish the prevalence and
levels of OTA in local foodstuffs, particularly rice, which is
a staple food in most communities along the West African
nations. Rice is a very good substrate for colonization by A,
ochraceus producing strains and is naturally contaminated
by the spores of this fungus during storage [49]
How to Cite this Article: Felixtina Jonsyn-Ellis , “Ochratoxin a: Any Cause for Concern in Sub Saharan Africa? ,”Science Journal of Environmental Engineering Research,
Volume 2012, Article ID sjeer-109, 5 Pages, 2012. doi: 10.7237/sjeer/109
Page 4
Despite the fact that the role of OTA as the causative agent
of human diseases such as BEN is not well defined,
nonetheless extensive experiments on animals have
provided conclusive evidence of its nephrotoxicity,
carcinogenicity, teratogenicity and immunosuppressive
nature. As OTA is now classified as a 2B carcinogen (possible
carcinogen-according to IARC) - it is therefore imperative
for African Countries to empower their scientists to:
Ÿ Conduct studies to determine the occurrence and
ecology of ochratoxigenic fungi and toxins in local as
well as imported foods such as rice
Ÿ Carry out epidemiological investigation to determine
the extent of human exposure to OTA and document
cases of chronic renal diseases
Ÿ Understand and appreciate the gravity of mycotoxin
(ochratoxin, aflatoxin and fumonisin) in the food chain
and conduct massive awareness campaign.
Ÿ Create a National Mycotoxin Awareness Study
Network, similar to the one is Nigeria; in order to forge
a North -South and South-South network to (a)
standardize methods of surveys and determination of
these mycotoxins (b) establish regulations and
guidelines on specific mycotoxins (c) conduct
collaborative research and (d) promote capacity
building.
Ÿ Search for local foodstuffs with antioxidant properties.
Vitamin A, C & E are all known to have ameliorating
effects on the toxicity of certain mycotoxins [50]
Ÿ Investigate the effect of climate change on the
production and accumulation not only of ochratoxin but
all major mycotoxins.
Ÿ With the full support and collaboration of the Ministry
of Health, establish a Cancer Registry
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How to Cite this Article: Felixtina Jonsyn-Ellis , “Ochratoxin a: Any Cause for Concern in Sub Saharan Africa? ,”Science Journal of Environmental Engineering Research,
Volume 2012, Article ID sjeer-109, 5 Pages, 2012. doi: 10.7237/sjeer/109